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Updated: Oct 19, 2025
Isolation and In Vitro Culture of Murine and Human Alveolar Macrophages
Published on: April 20, 2018
The antimicrobial peptide S100A8/A9 produced by airway epithelium functions as a potent and direct regulator of
Wioletta Skronska-Wasek1,2, Sibel Durlanik3, Huy Quang Le2
1Cancer Immunology and Immune Modulation, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach, Germany wioletta.skronska-wasek@boehringer-ingelheim.com.
Background:
Elevated counts of alveolar macrophages and attenuated phagocytic capacity are associated with chronic obstructive pulmonary disease (COPD). Factors governing macrophage phagocytosis are poorly understood. In this study we aimed to compare the influence of airway epithelial cell secretions from individuals with COPD and without COPD (non-COPD) on macrophage phagocytic activity, and the role of antimicrobial peptides (AMPs).
Methods:
Supernatants from non-COPD and COPD small airway epithelial cell (SAEC) cultures exposed to non-typeable Haemophilus influenzae (NTHi) were applied to human monocyte-derived macrophages (MDMs) to assess their influence on phagocytosis. SAECs were analysed for changes in AMP expression by quantitative reverse transcription PCR, and the influence of select AMPs on macrophage phenotype and function was assessed by flow cytometry and metabolic activity assay.
Results:
Secretions from the apical and basolateral surface of NTHi-exposed SAECs from non-COPD donors elicited superior phagocytic capacity in MDMs. Moreover, NTHi exposure led to a rapid increase in the expression of a range of AMPs by non-COPD SAECs, but this response was delayed in COPD SAECs. We demonstrate that treatment with AMPs β-defensin 2 and S100 calcium binding protein A8/S100 calcium binding protein A9 (S100A8/A9) improved the phagocytic capacity of MDMs. In-depth analysis of the influence of S100A8/A9 on MDMs revealed a role for this AMP in macrophage phenotype and function. Furthermore, we show that the expression of S100A8 and S100A9 is directly regulated by WNT/β-catenin signalling, a known deregulated pathway in COPD.
Conclusion:
In conclusion, for the first time, we demonstrate that airway epithelium from patients with COPD has a reduced capacity to support the phagocytic function of macrophages in response to acute NTHi exposure, and we identify the WNT/β-catenin signalling-modulated and epithelium-derived S100A8/A9 as a potent regulator of macrophage phenotype and function.
Insights
Airway epithelial cells from COPD patients impair macrophage phagocytosis due to delayed antimicrobial peptide production. S100A8/A9, regulated by WNT/β-catenin signaling, improves macrophage function in chronic obstructive pulmonary disease.
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Chronic obstructive pulmonary disease (COPD) is linked to increased alveolar macrophages with reduced phagocytosis.
- The mechanisms regulating macrophage phagocytosis in COPD are not fully understood.
Purpose of the Study:
- To compare the effect of airway epithelial cell secretions from COPD and non-COPD individuals on macrophage phagocytic activity.
- To investigate the role of antimicrobial peptides (AMPs) in this process.
Main Methods:
- Supernatants from non-typeable *Haemophilus influenzae* (NTHi)-exposed small airway epithelial cells (SAECs) from COPD and non-COPD donors were applied to macrophages.
- AMP expression in SAECs was quantified, and the impact of specific AMPs on macrophage function was assessed.
Main Results:
- Secretions from non-COPD SAECs enhanced macrophage phagocytosis more effectively than those from COPD SAECs.
- NTHi exposure induced a faster AMP response in non-COPD SAECs compared to COPD SAECs.
- AMPs like β-defensin 2 and S100A8/A9 improved macrophage phagocytic capacity, with S100A8/A9 influencing macrophage phenotype and function.
Conclusions:
- Airway epithelium from COPD patients exhibits diminished support for macrophage phagocytosis against NTHi.
- Epithelium-derived S100A8/A9, modulated by WNT/β-catenin signaling, is identified as a key regulator of macrophage function in COPD.
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